Colon lavage system

ABSTRACT

The present invention provides compositions, systems, kits, and methods for preparation prior to a colonoscopy or other gastrointestinal procedure. In particular, the present invention provides a colon lavage system comprising an aqueous portion and a solid portion.

The present application is a continuation of U.S. application Ser. No.16/786,541, filed Feb. 10, 2020, which is a continuation of U.S.application Ser. No. 14/285,224, filed May 22, 2014, now U.S. Pat. No.10,555,970, issued Feb. 11, 2020, which is divisional of U.S. patentapplication Ser. No. 12/763,821, filed Apr. 20, 2010, now U.S. Pat. No.8,778,306, issued Jul. 15, 2014, which claims priority to U.S.Provisional Patent Application Ser. No. 61/171,337, filed Apr. 21, 2009,each of which are herein incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention provides compositions, systems, kits, and methodsfor preparation prior to a colonoscopy or other gastrointestinalprocedure. In particular, the present invention provides a colon lavagesystem comprising an aqueous portion and a solid portion.

BACKGROUND OF THE INVENTION

Screening colonoscopy is seen as delivering among the best returns onpublic investment (Maciosek et al. Am J Prev Med 2006; 31:52-61, hereinincorporated by reference in its entirety). Despite a growing body ofdata, only half of adults in the United States for whom a colonoscopy isrecommended undergo the procedure (Cancer Prevention & Early DetectionFacts and Figures 2006, American Cancer Society, herein incorporated byreference in its entirety). One of the major barriers to compliance isthe unpleasantness of the preparation procedure (aka gastrointestinallavage, colon gavage, colonoscopy prep, etc.)) (Harewood et al. Am JGastroenterol 2002; 97: 3186-94, herein incorporated by reference in itsentirety). Preparation of the colon for optical colonoscopy is importantfor an accurate and efficient exam. It is not surprising that poor prepsresult in higher miss rates for significant lesions (Froehlich et al.Gastrointest Endosc 2005; 61:378-84, herein incorporated by reference inits entirety), and are a major cause of lengthier, time-consuming exams(Rex et al. Am J Gastroenterol 2002; 97:1698-1700, herein incorporatedby reference in its entirety).

There are a number of ways to cleanse the colon, each with advantagesand disadvantages. The physician must balance the factors of patientsafety, patient tolerability, and quality of the prep. For example,growing data on the risks of sodium phosphate preps has temperedenthusiasm for these types preps. Purgatives can be based on magnesiumsalts, sodium phosphate, or buffered saline solution with polyethyleneglycol (PEG). Bisacodyl is sometimes added to the regimen to stimulatecolonic motility. The downside of adding Bisacodyl to a cleansingregimen is that it may cause additional nausea and cramps. An overviewof the current state of colonoscopy prep products is as follows:

Magnesium Salt Preparations

Magnesium salts, such as Magnesium Citrate are known to stimulatecolonic mucosal ion secretion (Izzo et al. Br J Pharmacol. 1994September; 113 (1):228-32, herein incorporated by reference in itsentirety). Few gastroenterologists still use over-the-counter MagnesiumCitrate solution as a prep. The only Magnesium-based solution designedfor colonoscopy preparation is the LOSO PREP, a proprietary kit marketedby the EZ-EM Corporation. Magnesium Citrate is provided as a dry powderin a pre-measured pouch that is reconstituted with water or as aconcentrated solution that is diluted before use. It is marketed withfour 5 mg Bisacodyl tablets to take during the prep and a single 10 mgBisacodyl suppository to use the morning of the procedure. Studies haveexamined its efficacy as bowel prep and show results similar toPEG-based preps with better tolerability (Delegge et al. AlimentPharmacol Ther 2005; 21: 1491-1495, Rapier et al. GastroenterologyNursing 2006; 29 (4):305-308, herein incorporated by reference in theirentireties). This has been studied in combination with an extremely lowresidue diet (NUTRA PREP, EZ-EM Corporation) with similar results.Electrolyte imbalances can occur if sufficient clear liquids are notconsumed during the prep.

Sodium Phosphate Preparations

Sodium phosphate works as an osmotic agent and draws fluid into thecolon, resulting in a purgative effect. Sodium Phosphate can be given asa solution (FLEET PHOSPHO-SODA EZ-PREP) or as tablets (VISICOL ANDOSMOPREP). They are among the best tolerated colon preps from apatient's point of view (Hookey et al. Am J Gastroenterol. 2004; 99(11):2217-22, Lichtenstein et al. Aliment Pharmacol Ther. 2007; 26(10):1361-1370, herein incorporated by reference in their entireties).It is critical for patients to drink sufficient quantities of dearliquids during these preps to ensure that the cathartic effect does notdehydrate them during the prep. The FLEET PHOSPHO-SODA PREP instructspatients to drink 24 ounces of fluid with the first dose ofPHOSPHO-SODA, at least 24 ounces of clear liquids in between doses, and24 ounces with the second dose. Patients who do not drink at least therequired 2.1 liters of fluid during their prep are at significant riskof renal and electrolyte problems as a result of the prep.

During routine use of sodium phosphate preps, some of the phosphate isabsorbed, and there is growing evidence that this may damage the kidney.Beginning in 2003, reports began to emerge about acute and chronicphosphate nephropathy in patients receiving phosphate-based preps,namely FLEETS PHOSPHO-SODA and VISICOL (Desmeules et al. NEJM. 200:349(10):1006-7, herein incorporated by reference in its entirety). The FDAnow lists on their website more than thirty cases of renal injuryassociated with the use of phosphate salts for colon preparation. TheFDA reports were associated with higher dosing regimens for phosphatepreps (60 or more grams of sodium phosphate). No reports were receivedregarding the use of OSMOPREP®, which contains 48 grams of sodiumphosphate. All regimens have now been brought below 60 grams of sodiumphosphate. More recent studies in the Nephrology literature describe arelative risk for acute kidney injury at 1.5 to 3.6 times that ofcontrols in those patients who have taken a phosphate-based colon prep(Markowitz et al. J Am Soc Nephrol 2005; 16:3389-96, herein incorporatedby reference in its entirety). Patients who are at increased risk forthis complication include people over the age of 57, and those withsignificant co-morbidity including hypertension, pre-existing CKD, andthose patients taking either angiotensin converting enzyme (ACE)inhibitors or angiotensin receptor blockers (ARB). Because of theproblems arising with sodium phosphate preps, training programs such asMayo Clinic and University of Pennsylvania have relegated these preps tosecondary status. Most recently, in December 2008, the FDA appliedblack-box warnings to VISICOL and OSMOPREP to highlight the risk forserious renal injury. Shortly after that, the C.B. Fleet Companyvoluntarily withdrew FLEETS PHOSPHO-SODA from the market due to its riskfor renal injury when used as a colon prep.

Polyethylene Glycol (PEG) Preparations

Buffered saline solutions with PEG have been available for almost thirtyyears. While providing less risk to the patient with regard to fluid andelectrolyte balance, the sheer volume of fluid to drink coupled with thepoor palatability of some of these solutions have made them unpopularamong the initiated. PEG based products are marketed under a variety oftrade names (GO-LYTELY, COLYTE, NULYTELY, HALFLYTELY, GLYCOPREP, andMOVIPREP (see e.g., U.S. Pat. No. 7,169,381, herein incorporated byreference in its entirety)). COLYTE and GOLYTELY are the prototypical4-liter colon gavage preps. The salty taste, nausea, and cramps causethe majority of patient complaints. NULYTELY was formulated as animprovement over GOLYTELY® with the deletion of Sulfate as an osmoticagent, increasing the PEG concentration to increase its osmotic effect,and the addition of flavor packs to improve palatability. The volumeremains 4 liters. The latest iterations of PEG-based preps areHALFLYTELY and MOVIPREP. Both are 2-liter prep solutions. HALFLYTELY ismarketed with two 5 mg Bisacodyl tablets to take during the prep toenhance colonic emptying. MOVIPREP does not require Bisacodyl but doesrequire an additional liter of clear liquid be consumed during the prep.In general, the 2-liter PEG preps are better tolerated but not quite ascleansing as the 4 liter PEG preps.

One trend that is gaining popularity is the split-dosing schedule,wherein only half of the prep is taken the night before the procedure,and the remainder is taken early in the morning prior to the procedure.The split schedule improves tolerability for patients (Aoun et al.Gastrointest. Endosc. 2005; 62 (2):213-8, herein incorporated byreference in its entirety). The diminished volume of any one dosereduces nausea and cramps. Ileal effluent (mucous, bile, and sloughedcells) may accumulate in the cecum and right colon overnight aftercompletion of a prep. This material is often washed away by the morningdose in the split dose schedule. The split schedule requires that thepatient get up early to take their morning dose 3 to 5 hours prior totheir procedure. Some of the newer preps are designed as a split dose(FLEET'S PHOSPHO-SODA, VISICOL, OSMOPREP, and MOVIPREP). The 4-liter PEGpreps can also be given as a split dose, usually 3 liters in the eveningand 1 liter in the early morning.

Improving the diet prior to and during the prep may improve patienttolerance. There is some data indicating that the use of extremely lowresidue diets during the day of the prep (the day prior to thecolonoscopy) instead of a clear liquid diet only may improve thetolerability of the regimen without diminishing the quality of coloniccleansing (Scott et al. Gastroenterol. Nurs. 2005; 28:133-139, hereinincorporated by reference in its entirety). A pre-packaged low residuediet is marketed by E-Z-EM under the label NUTRA-PREP.

Typical gastrointestinal lavage formulations are described in US Pat.App. No. 2007/0098764, US Pat. App. No. 2007/0298008, Fordtran et al.Gastroenterology 1990:98:11-16, Ernstoff et al. Gastroenterology1983:84:1512-6, Davis et al. Gastroenterology. 1980:78:991-995, hereinincorporated by reference in their entireties.

What are needed are improved systems and methods that improve patienttolerance and maintain safety and efficacy.

SUMMARY

In some embodiments, the present invention provides a kit comprising aplurality of individually packaged doses of a palatable osmotic agent,to be administered in aqueous solution, and a plurality of doses ofelectrolytes. In some embodiments, the osmotic agent comprises PEG. Insome embodiments, the electrolytes comprise sodium bicarbonate, sodiumchloride, and potassium chloride. In some embodiments, the electrolytesfurther comprise sodium sulfate. In some embodiments, the electrolytescomprise ascorbic acid and/or sodium ascorbate. In some embodiments, theelectrolytes further comprise salts of magnesium, such as magnesiumsulfate or magnesium citrate. In some embodiments, the plurality ofdoses of electrolytes comprises pills, capsules, tablets, gel-caps,gel-caps filled with a paste or suspension, micro-encapsulated salts foradministration as a capsule or suspended in a liquid. In someembodiments, a kit of the present invention further comprises aplurality of flavored drink mix doses or other flavorant packages. Insome embodiments, the plurality of individually packaged doses ofpalatable osmotic agent comprises 4-12 doses of osmotic agent, althoughhigher or lower amounts may be used. In some embodiments, the pluralityof doses of electrolytes comprises 2-8 doses per dose of osmotic agent,although higher or lower amounts may be used.

In some embodiments, the present invention provides a method forpreparing a subject for a colon-related procedure comprising one or moreof the steps of: (a) providing a plurality of individually packagedosmotic agent doses and a plurality of individually packaged electrolytedoses, (b) dissolving one or more of a plurality of osmotic agent dosesin water or other solvent (e.g., other aqueous solvent), (c)administering one or more of the plurality of osmotic agent dosesdissolved in water or other solvent to a subject, (d) administering oneor more of a plurality of electrolyte doses to a subject, (e) repeatingsteps (b)-(d) until all of the plurality of osmotic agent doses and allof the plurality of electrolyte doses have been ingested by the subject,(f) passing stool from the colon of said subject, (g) analyzing stoolfrom the subject, and (h) carrying out a diagnostic or surgicalprocedure on the subject. In some embodiments, the method comprises orconsists of steps (a)-(e). In some embodiments, the palatable osmoticagent comprises PEG. In some embodiments, the electrolytes comprisesodium bicarbonate, sodium chloride, and potassium chloride. In someembodiments, the electrolytes further comprise sodium sulfate. In someembodiments, the electrolytes comprise ascorbic acid and/or sodiumascorbate. In some embodiments, the electrolytes further comprise saltsof magnesium, such as magnesium sulfate or magnesium citrate. In someembodiments, the plurality of doses of electrolytes comprises pills,capsules, tablets, gel-caps, gel-caps filled with a paste or suspension,micro-encapsulated salts for administration as a capsule or suspended ina liquid. In some embodiments, a method of the present invention furthercomprises providing a plurality of flavorant packages, includingflavored drink mix doses, wherein the flavor mix is dissolved in wateror other solvent with the plurality of purgative doses. In someembodiments, passing stool from the colon of the subject comprisesevacuating the colon of digested or undigested food and stool.

DETAILED DESCRIPTION OF EMBODIMENTS

In some embodiments, the present invention provides compositions,systems, kits, and methods for patient preparation prior to acolon-related medical procedure (e.g. colonoscopy). In particular, insome embodiments, the present invention provides a colon lavage systemcomprising an aqueous portion and a solid portion. In some embodiments,the present invention provides a colon lavage system that employs bothaqueous solution and capsules or pills or tablets or other deliverymodes to improve palatability over current PEG (polyethyleneglycol)-based preps and improve safety over current tablet preps. Insome embodiments, the present invention provides improved patientcompliance with colon-prep procedure. In some embodiments, the presentinvention provides improved accuracy for colonoscopy and othergastrointestinal procedures. In some embodiments, the present inventionprovides a multi-component system (e.g. 2 components, 3 components,greater than 3 components, etc.). In some embodiments, the presentinvention provides two components: (1) a palatable osmotic agent, and(2) an electrolyte component. In some embodiments, the present inventionprovides two components: (1) a plurality of osmotic agent doses, and (2)a plurality electrolyte doses. In some embodiments, the presentinvention provides two components: (1) an aqueous PEG solution, and (2)salt pills. In some embodiments, the salt pills may contain electrolytesthat may act as an osmotic agent in the gut, such as sulfate saltsand/or magnesium salts.

In some embodiments, the present invention provides a palatable osmoticagent component. In some embodiments, the present invention provides astimulant, lubricant, and/or saline laxatives to evacuate the colon. Insome embodiments, an additional purgative of the present invention maybe selected from, but is not limited to bulk-producing agents, stoolsofteners, surfactants, lubricants, emollients, hydrating agents,osmotics, saline solutions, hyperosmotics (e.g. PEG), stimulants,irritants, serotonin agonists, etc. In some embodiments, the presentinvention serves to hasten the elimination of digested and undigestedremains of food in the large intestine and colon. In some embodiments,the purgative of the present invention is configured to induce bowelmovement in a desired time (e.g. <30 minutes, 1 hour, 2 hours, 3 hours,4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11hours, 12 hours, >12 hours, etc.).

In some embodiments, the palatable osmotic agent component of presentinvention is a polyethylene glycol (PEG) component. In some embodiments,the present invention comprises a polyethylene oxide) (PEO) orpolyoxyethylene (POE) component. In some embodiments, PEG oligomersand/or polymers of the present invention have a molecular weight oraverage molecular weight below 20,000 g/mol (e.g. <20000 g/mol, <15000g/mol, <12000 g/mol, <10000 g/mol, <8000 g/mol, <6,000 g/mol, <4,000g/mol, <2000 g/mol, <1000 g/mol, etc.). In some embodiments, the PEGoligomers and/or polymers of the present invention have a molecularweight or average molecular weight above 105 g/mol (e.g. >200g/mol, >300 g/mol, >400 g/mol, >500 g/mol, >750 g/mol, >1000g/mol, >2000 g/mol, >4000 g/mol, >6000 g/mol, etc.). In someembodiments, the PEG oligomers and/or polymers of the present inventionhave a molecular weight or average molecular weight greater than orequal to 1450 daltons and less than or equal to 8000 daltons. In someembodiments, the PEG oligomers and/or polymers of the present inventionhave a molecular weight or average molecular weight of approximately3350 daltons or of 3350 daltons. In some embodiments, the presentinvention provides PEG dissolved in water or aqueous solution. In someembodiments, the present invention provides thy PEG configured to bedissolved in water or aqueous solution. In some embodiments, the presentinvention provides a concentrated PEG solution configured to be dilutedin water or aqueous solution. In some embodiments, PEG of the presentinvention is low toxicity. In some embodiments, the PEG component of thepresent invention serves as a laxative and/or purgative (e.g. taken toinduce bowel movements and/or to loosen the stool). In some embodiments,PEG is a hyperosmotic agent. In some embodiments, the purgativecomponent consists of PEG in either dry power form or dissolved in water(i.e., consists of PEG and water).

In some embodiments, the palatable osmotic agent component does notcontain salt or is substantially free of salt. In some embodiments, thepalatable osmotic agent component does not contain any salt other thansalt that is provided as part of the PEG component (e.g., as a byproductof PEG manufacture). In some embodiments, the palatable osmotic agentcomponent is free from or substantially free from or functionally free(i.e., salts are present at a concentration insufficient to elicit abenefit to colon lavage procedures) from one or more of the salts:sodium sulfate, sodium bicarbonate, sodium chloride, sodium phosphate(e.g. monosodium phosphate, disodium phosphate, trisodium phosphate,etc.) potassium bicarbonate, potassium chloride, potassium phosphate,potassium sulfate, magnesium sulfate, magnesium bicarbonate, magnesiumchloride, magnesium phosphates, calcium bicarbonate, calcium chloride,calcium phosphate, calcium sulfate, ascorbic acid, and sodium ascorbate.

In some embodiments, the present invention provides an electrolytecomponent. In some embodiments, the electrolyte component comprises orconsists of one or more salts. In some embodiments, the electrolytecomponent is provided in a solid form suitable for oral administrationin solid form. In some embodiments, the electrolyte component of thepresent invention comprises one or more cations (e.g., sodium,potassium, magnesium, calcium, etc.). In some embodiments, theelectrolyte component comprises the anions (e.g., bicarbonate, chloride,phosphate, sulfate, etc.). In some embodiments, the electrolytecomponent comprises or consists of sodium bicarbonate, sodium chloride,and potassium chloride. In some embodiments, the electrolyte componentcomprises or consists of sodium sulfate, sodium bicarbonate, sodiumchloride, and potassium chloride. In some embodiments, the electrolytecomponent of the present invention comprises or consists of sodiumsulfate, sodium bicarbonate, sodium chloride, sodium phosphate (e.g.monosodium phosphate, disodium phosphate, trisodium phosphate, etc.),potassium bicarbonate, potassium chloride, potassium phosphate,potassium sulfate, magnesium sulfate, magnesium bicarbonate, magnesiumchloride, magnesium phosphates, calcium bicarbonate, calcium chloride,calcium phosphate, calcium sulfate, ascorbic acid, sodium ascorbate,etc. In some embodiments, the electrolyte component comprises 30 gramsor less Sodium sulfate in tablet/capsule form to be ingested with eachliter of aqueous osmotic agent (e.g. 30 grams . . . 25 grams . . . 20grams . . . 15 grams . . . 10 grams . . . 5 grams . . . 0 grams, etc.).In some embodiments, the electrolyte component comprises 10 grams orless Sodium bicarbonate in tablet/capsule form to be ingested with eachliter of aqueous purgative (e.g. 10 grams . . . 8 grams . . . 6 grams .. . 4 grams . . . 2 grams . . . 0 grams, etc.). In some embodiments, theelectrolyte component comprises 20 grams or less Sodium chloride intablet/capsule form to be ingested with each liter of aqueous purgative(e.g. 20 grams . . . 16 grams . . . 12 grams . . . 8 grams . . . 4 grams. . . 0 grams, etc.). In some embodiments, the electrolyte componentcomprises 5 gram or less Potassium chloride in tablet/capsule form to beingested with each liter of aqueous purgative (e.g. 5 gram . . . 4 grams. . . 3 grams . . . 2 grams . . . 1 grams . . . 0 grams, etc.). In someembodiments, the electrolyte component comprises 20 grams or less Sodiumascorbate in tablet/capsule form to be ingested with each liter ofaqueous purgative (e.g. 20 grams . . . 16 grams . . . 12 grams . . . 8grams . . . 4 grams . . . 0 grams, etc.). In some embodiments, theelectrolyte component comprises 20 grams or less Ascorbic acid intablet/capsule form to be ingested with each liter of aqueous purgative(e.g. 20 grams . . . 16 grams . . . 12 grams . . . 8 grams . . . 4 grams. . . 0 grams, etc.). In some embodiments, the electrolyte componentcomprises 10 grams or less Magnesium citrate in tablet/capsule form tobe ingested with each liter of aqueous purgative (e.g. 10 grams . . . 8grams . . . 6 grams . . . 4 grams . . . 2 grams . . . 0 grams, etc.). Insome embodiments, the electrolyte component comprises 100 grams or lesssalt in tablet/capsule form to be ingested with each liter of aqueouspurgative (e.g. 100 grams . . . 80 grams . . . 60 grams . . . 40 grams .. . 20 grams . . . 0 grams, etc.). In some embodiments, the electrolytecomponent is configured to maintain proper electrolyte levels in asubject undergoing a colon lavage procedure. In some embodiments, theelectrolyte component is configured to maintain proper electrolytelevels in a subject undergoing purgative preparation for colonoscopy. Insome embodiments, the electrolyte component is administered in a seriesof doses and is configured to mix in the stomach of the subject. In someembodiments, the electrolyte component is configured to mix in thestomach of a subject to provide an electrolyte solution which isapproximately iso-osmotic with plasma (e.g. 230 mM to 330 mM, 270 mM to290 mM, 280 mM, etc.). In some embodiments, the electrolyte component isconfigured to mix in the stomach of a subject to provide an electrolytesolution which is slightly hyper-osmolar with plasma (e.g. 280 mM to 400mM, etc.). In some embodiments, each dose of electrolytes (e.g. tablet,capsule, pill, etc.) comprises 300 mg to 1000 mg of solid material (e.g.electrolytes, filler, etc.) per dose (e.g. 300 mg . . . 400 mg . . . 500mg . . . 600 mg . . . 700 mg . . . 800 mg . . . 900 mg . . . 1000 mg,etc.). In some embodiments, the mass or volume of solid material perdose is selected to reach a balance between number of doses and size ofdoses to be administered to a subject. In some embodiments, theelectrolyte component is marketed as capsules, tablets, gel-caps, etc.to be combined by the purchaser with an over-the-counter osmotic agentsuch as PEG 3350.

In some embodiments, the present invention provides a palatable osmoticagent component and an electrolyte component in ingestible doses. Insome embodiments, the osmotic agent (e.g. PEG) is provided in a dry form(e.g. powder, granular, etc). In some embodiments, the osmotic agent(e.g. PEG) is provided in a thy volume configured to be dissolved in asolvent (e.g. water). In some embodiments, the osmotic agent (e.g. PEG)is provided in a dry volume configured to be dissolved in a convenientvolume (e.g. 250 ml, 500 ml, 1 L, 8 ounces, 16 ounces, 24 ounces, etc.)of solvent (e.g. water). In some embodiments, the osmotic agent (e.g.PEG) is provided in aliquots based on weight (e.g. 5 grams . . . 10grams . . . 15 grams . . . 20 grams . . . 25 grams . . . 29.5 grams . .. 35 grams . . . 40 grams . . . 45 grams . . . 50 grams . . . 55 grams .. . 60 grams . . . etc.). In some embodiments, an amount of osmoticagent (e.g. PEG) is configured to be dissolved in a specified volume ofwater (e.g. 15 grams PEG in 8 ounces of water, 29.5 grams of PEG in 500ml of water, 52.5 grams of PEG in 500 ml water, 60 grams of PEG in 1 Lof water, etc.). In some embodiments, the palatable osmotic agent (e.g.PEG) can be dissolved in more solvent (e.g. water) to create lessconcentrated solution to better mask the presence of the osmotic agentin the solution. In some embodiments, the osmotic agent (e.g. PEG) canbe dissolved in less solvent (e.g. water) to create more concentratedsolution so a subject can drink a smaller volume of liquid. In someembodiments, a volume of osmotic agent (e.g. PEG) is dissolved in avolume of solvent (e.g. water) appropriate for eliciting the desiredpurging effect. In some embodiments, the present invention provides aplurality of doses of osmotic agent, each to be dissolved in separatevolumes of solvent (e.g. 2 doses, 3 doses, 4 doses, 5 doses, 6 doses, 7doses, 8 doses, 9 doses, 10 doses, >10 doses, etc.). In someembodiments, the cumulative amount of the provided doses is equal to thetotal amount of osmotic agent to be taken in a prep (e.g., 4 liters, 3liters, 2 liters, etc.).

In some embodiments, the present invention provides a flavorant. Theflavorant may be formulated as part of the osmotic agent component.Likewise, the flavorant may be provided separately and mixed with theosmotic agent component prior to administration. The flavorant may beprovided as a solid (e.g., powder) or may be a liquid. In someembodiments, the flavorant is provided in liquid form and acts as theliquid carrier for delivery of the osmotic agent component. In someembodiments, dry osmotic agent component (e.g., PEG) and dry flavorantare added to water prior to administration. The present invention is notlimited by the nature of the flavorant. In some embodiments, theflavorant is a commercially available drink mix material (e.g. CRYSTALLIGHT, HI-C, similar drink mixes, etc.). In some embodiments, thepresent invention provides a plurality of flavored drink mix aliquots inindividual packages. In some embodiments, individual packages offlavored drink mix are configured to flavor a volume of water. In someembodiments, individual packages of flavored drink mix are configured toflavor a volume of water corresponding to the volume of water requiredto dissolve a dose of osmotic agent (e.g. PEG) provided by the presentinvention (e.g. 250 ml . . . 500 ml . . . 1000 ml . . . 2000 ml . . .4000 ml . . . etc.). In some embodiments, flavored drink mix produces aflavored drink when dissolved in an appropriate volume of water. In someembodiments, flavored drink mix makes thinking water (e.g. a largevolume of water, water with dissolved osmotic agent, etc.) moreacceptable (e.g. palatable, enjoyable, etc.) to a subject. In someembodiments, flavored drink mix can be provided in any suitable flavor(e.g. cherry, strawberry, watermelon, grape, lemon-lime, banana, icedtea, lemonade, apple, orange, etc.). In some embodiments, the presentinvention provides a variety of different flavors of flavored drink mixto allow a subject to flavor successive doses of osmotic agent dissolvedin water with different flavors, reducing or avoiding taste fatigue. Insome embodiments, flavored water with dissolved osmotic agent isindistinguishable or nearly undistinguishable from flavored waterwithout dissolved osmotic agent (e.g. PEG). In some embodiments, othercomponents, such as colorants, alcohol, or medications are provided withthe osmotic agent administration.

In some embodiments, the present invention provides individuallypackaged doses of PEG (e.g. 29.5 grams) that can be dissolved into 0.5liters of water (e.g. standard sized water bottle). In some embodiments,the above PEG and water solution is consumed with or without flavoring(e.g. CRYSTAL LITE or similar). In some embodiments, a plurality ofdoses (e.g. 29.5 grams of PEG in 0.5 liters of water) are consumed toyield a total volume which is appropriate for a patients size, age,health, and/or physical characteristics (e.g. 1 liter (2 doses), 1.5liters (3 doses), 2 liters (4 doses), 2.5 liters (5 doses), 3 liters (6doses), 3.5 liters (7 doses), 4 liters (8 doses), 4.5 liters (9 doses),5 liters (10 doses), 5.5 liters (11 doses), 6 liters (12 doses), 6.5liters (13 doses), 7 liters (14 doses), 7.5 liters (16 doses), 8 liters(16 doses), 8.5 liters (17 doses), 9 liters (18 doses), 9.5 liters (19doses), 10 liters (20 doses), >10 liters (>20 doses), etc.). In someembodiments, the present invention provides individually packaged dosesof PEG (e.g. 52.5 grams) that can be dissolved into 0.5 liters of water(e.g. standard sized water bottle). In some embodiments, the above PEGand water solution is consumed with or without flavoring (e.g. CRYSTALLITE or similar). In some embodiments, a plurality of doses (e.g. 29.5grams of PEG in 0.5 liters of water) are consumed to yield a totalvolume which is appropriate for a patients size, age, health, and/orphysical characteristics (e.g. 1 liter (2 doses), 1.5 liters (3 doses),2 liters (4 doses), 2.5 liters (5 doses), 3 liters (6 doses), 3.5 liters(7 doses), 4 liters (8 doses), 4.5 liters (9 doses), 5 liters (10doses), 5.5 liters (11 doses), 6 liters (12 doses), 6.5 liters (13doses), 7 liters (14 doses), 7.5 liters (16 doses), 8 liters (16 doses),8.5 liters (17 doses), 9 liters (18 doses), 9.5 liters (19 doses), 10liters (20 doses), >10 liters (>20 doses), etc.). In some embodiments,PEG dose size and water volume are adjusted for ease of packaging,marketing, ingestion, etc. In some embodiments, the number of doses(e.g., half liter doses) is selected for a patient based on their size,age, gender, etc. Thus, in some embodiments, some patients are notrequired to consume 4 liters of product, but can consume a lesser, morepalatable amount.

In some embodiments, the present invention provides capsules, pills,gel-caps, micro-encapsulated granules, or tablets containing saltsselected from but not limited to sodium sulfate, sodium bicarbonate,sodium chloride, and potassium chloride. In some embodiments, apreselected number of salt doses (e.g. capsules, etc.) are ingested by asubject with each dose of dissolved osmotic agent (e.g. PEG solution)(e.g. 1 salt dose/1 PEG dose, 2 salt doses/1 PEG dose, 2 salt doses/1PEG dose, 3 salt doses/1 PEG dose, 4 salt doses/1 PEG dose, 5 saltdoses/1. PEG dose, 6 salt doses/1 PEG dose, 7 salt doses/1 PEG dose, 8salt doses/1 PEG dose, 9 salt doses/1 PEG dose, 10 salt doses/1 PEGdose, >10 salt doses/1 PEG dose, etc.). In some embodiments, apreselected number of salt doses (e.g. capsules, etc.) are ingested by asubject with each 0.5 liter dose of PEG solution. In some embodiments,mixing of the PEG and salts occurs in the stomach producing a PEG andsalt solution. In some embodiments, a PEG and salt solution produced bymixing a plurality of osmotic agent components (e.g. PEG component) anda plurality of salt components (e.g. electrolytes) with the specifiedvolume of water results in a solution of similar or identical makeup andconcentration to standard formulations in use (e.g. MOVIPREP, GOLYTELY,NULYTELY, etc.).

In some embodiments, commonly used or standard formulations of osmoticagent and salt solutions comprise 100 g/L PEG-3350, 7.5 g/L sodiumsulfate, 2.69 g/L sodium chloride, and 1.015 g/L potassium chloride. Insome embodiments, the proceeding concentrations are present in 0.5 L,1.0 L, or 2 L doses. In some embodiments, commonly used or standardformulations of purgative and salt solutions comprise 60 g/L PEG-3350,5.68 g/L sodium sulfate, 1.46 g/L sodium chloride, 1.68 g/L sodiumbicarbonate, and 0.745 g/L potassium chloride. In some embodiments, theproceeding concentrations are present in 0.5 L, 1.0 L, or 2 L doses. Insome embodiments, a mixed solution of commonly used or standardformulations of PEG and electrolytes comprises 125 mEq/L sodium, 10mEq/L potassium, 20 mEq/L bicarbonate, 80 mEq/L sulfate, 35 mEq/Lchloride, and 18 mEq/L polyethylene glycol-3350.

In some embodiments, the present invention provides compositions,systems, kits, and methods for patient preparation prior to acolon-related or gastrointestinal medical procedure. In someembodiments, the present invention provides compositions, systems, kits,and methods for use preparative use prior to gastrointestinal proceduresincluding but not limited to colonoscopy, capsule endoscopy, single- anddouble-balloon enteroscopy, endoluminal gastroplication, endoscopicultrasound (EUS), esophagogastroduodenoscopy (EGD), endoscopicretrograde cholangiopancreatography (ERCP), esophageal pH exam, flexiblesigmoidoscopy (Flex Sig), hydrogen breath test, liver biopsy,percutaneous endoscopic gastrostomy (PEG), biofeedback for anorectaldysfunction, intraoperative radiation therapy (IORT), diagnostic GIradiology, including barium enema, CT colonography, CT enterography, MRcolonography, and MR enterography; surgical procedures including, butnot limited to laparoscopic cholecystectomy (Gallbladder Removal),colectomy, hysterectomy, hemorrhoidectomy, herniorrhaphy, and NOTES(natural orifice transluminal endoscopic surgery).

In some embodiments, the present invention provides compositions,systems, kits, and methods for clearing digested and/or undigested foodand/or stool from the colon and/or other portions of thegastrointestinal for health reasons, to restore health, to remove toxins(e.g. pollution, secondary smoking, harmful chemicals, pesticides,etc.), as a remedy for ailments (e.g. constipation, hepaticencephalopathy, acne, candida, brain fog, sluggishness, colonicdysenertia, encopresis, constipative-predominant irritable bowelsyndrome (IBS-C)), and to prevent disease. In some embodiments, asubject being administered a composition, system, kit, or method of thepresent invention is a human (e.g. patient), animal, mammal, equine,bovine, cat dog, non human primate, rodent, etc.

In some embodiments, a composition, system, kits and/or method of thepresent invention may provided in any suitable manner or packaging. Insome embodiments, the palatable osmotic agent is provided in granular orpowder form in doses ready to be dissolved in clear liquid (e.g. wateror flavored drink). In some embodiments, doses of osmotic agent arepre-measured. In some embodiments, doses of osmotic agent are providedin doses to be dissolved in a specified volume of clear liquid (e.g. 250ml . . . 500 ml . . . 1000 ml . . . 1500 ml . . . 2000 ml, etc.). Insome embodiments, does of purgative are provided in individual bags,blister packs, cups, bottles, jars, envelopes, and/or containers, etc.In some embodiments, doses of osmotic agent are provided in a singlecontainer with multiple compartments. In some embodiments, a specificnumber of doses of purgative are provided in a kit or package accordingto patient specific criteria (e.g. age, size, weight, sex, medicalcondition, species, etc). In some embodiments, the number of osmoticagent doses are prepared and/or assembled by a pharmacist based onclinician and/or manufacturer instructions. In some embodiments, thenumber of osmotic agent (e.g. PEG) doses are preassembled into kitsand/or packages, and a proper kit or package is selected for a subjectbased on subject specific criteria (e.g. age, size, weight, sex, medicalcondition, species, etc.).

In some embodiments, electrolytes of the present invention are providedin a plurality of individual doses (e.g. pills, capsules, tablets,etc.). In some embodiments, electrolyte doses are manufactured bycombining the desired salts with a known carrier to form a solidpreparation suitable for oral administration. In general, thesecompounds are formulated with a pharmacologically acceptable liquid orsolid carrier, and a solvent, a dispersant, an emulsifier, a buffer, astabilizer, an excipient, a binder, a disintegrant, a lubricant, or thelike is added thereto as desired, so that a solid agent such as atablet, a granule, a powder, a fine powder, and a capsule, dry agent ora liquid agent. The carrier can be selected depending upon theadministration form and preparation form of the electrolyte dose. In thecase of an orally administered preparation comprising a solidcomposition, the preparation can be produced in the form of a tablet, apill, a capsule, a powder, a fine powder, a granule, a suspensioncontained within a gel-cap, or the like. In some embodiments, theelectrolytes are combined with, for example, starch, lactose,saccharose, mannitol, carboxymethyl cellulose, cornstarch, an inorganicsalt, or the like to aid in ease of administration. In addition, duringthe preparation of the orally administered preparation, a binder, adisintegrant, a surfactant, a lubricant, a fluidity accelerator, aflavor, a colorant, a perfume, and the like can be further formulated.Preferably, the salt isolated in manner so as not to elicit a tasteresponse from the subject. For example, digestable capsules may be usedto isolate the salt until reaching the stomach. In the case of forminginto a tablet or pill, electrolytes and accessory compounds or additivesare pressed into a tablet or pill of a suitable size for oraladministration. In the case of forming into a tablet or pill, forexample, the tablet or pill may be covered with a sugar-coating made ofsucrose, gelatin or hydroxypropyl cellulose, or with a film made of asubstance soluble in the stomach or intestine as desired. In the case ofa capsule, the electrolytes and any additional carriers and/or compoundsare contained in a plurality of synthetic capsules of suitable size fororal administration. Capsules dissolve upon entry into gastric juices,thereby releasing the electrolytes into the stomach.

In some embodiments, electrolytes of the present invention are providedin a plurality of individual doses (e.g. pills, capsules, tablets,etc.). In some embodiments, doses of electrolytes are provided inindividual packaging (e.g. blister packs). In some embodiments, some orall of the individual doses of electrolytes are packed together in amultidose container (e.g. bottle, jar, bag, blister pack, envelope,etc.). In some embodiments, individual doses of electrolytes are groupedtogether in larger multi-doses doses. In some embodiments, the presentinvention provides an equal number of multi-doses doses of electrolytesand does of osmotic agent (e.g. 4 groups of electrolyte pills and 4doses of osmotic agent). In some embodiments, doses of electrolytes areprovided in a single unit with multiple compartments. In someembodiments, a specific number of doses of electrolytes are provided ina kit or package according to patient specific criteria (e.g. age, size,weight, sex, medical condition, species, etc.). In some embodiments, thenumber of electrolyte doses are prepared and/or assembled by apharmacist based on clinician and/or manufacturer instructions. In someembodiments, the number of osmotic agent doses are preassembled intokits and/or packages, and a proper kit or package is selected for asubject based on subject specific criteria (e.g. age, size, weight, sex,medical condition, species, etc.).

In some embodiments, packages and/or kits of the present invention areprovided with flavored drink mix to make the osmotic agent solution morepalatable and/or drinkable. In some embodiments, doses of flavored drinkmix are pre-measured. In some embodiments, doses of flavored drink mixare provided in doses to be dissolved in a specified volume of clearliquid (e.g. 250 ml . . . 500 ml . . . 1000 ml . . . 1500 ml . . . 2000ml, etc.). In some embodiments, does of flavored drink mix are providedin individual bags, blister packs, cups, bottles, jars, envelopes,and/or containers, etc. In some embodiments, packages and/or kits of thepresent invention are provided with one or more different flavors offlavored drink mix (e.g. banana, cherry, strawberry, watermelon, rootbeer, passion fruit, berry, etc.). In some embodiments, flavored drinkmix is not provided with kits and/or packages of the present invention.In some embodiments, flavored drink mix to be used with the presentinvention must be provided by the patient or subject. In someembodiments, flavored drink mix is provided pre-dissolved in theappropriate volume of clear liquid (e.g. in dose-sized bottles). In someembodiments, an appropriate number of flavored drink mix doses areprovided to correspond to the number of osmotic agent doses.

In some embodiments, compositions, kits, and or systems of the presentinvention may be packaged in any suitable manner. In some embodiments,all components are packaged in a single container (e.g. box, bag,vessel, bottle, envelope, etc.). In some embodiments, components arepackaged in multiple containers. In some embodiments instructions areprovided with kits/packaging of the present invention. The instructionsmay include a CD-ROM or DVD (or other media source) providing a videoset of detailed instructions in addition to minted instructions. Thismay also include a link to a web site providing additional information,answers to frequently asked questions, troubleshooting, and alsotechnical support.

Typical products to illustrate the use of the invention:

The following illustrate the use of two different prototypes that arisefrom the patent. They differ by the amount of polyethylene glycol (PEG)ingested and also by the composition and number of salt capsules. Theworking names for the products are PEG and Hi-PEG. Lo-PEG is essentiallyindistinguishable from water in taste and consistency, but requires thatmore capsules be ingested. Hi-PEG has a mildly slippery, waxyaftertaste, but uses only half the number of salt capsules that Lo-PEGuses.

Contents of Lo-PEG kit:

8 Packets of PEG 3350, each containing 29.5 grams of PEG 3350

44 capsules, each containing:

Sodium sulfate, 0.517 grams per capsule

Sodium bicarbonate, 0.153 grams per capsule

Sodium chloride, 0.133 grams per capsule

Potassium chloride, 0.067 grams per capsule

In some embodiments, one kit will have 8 blister packs, each blisterpack containing a packet of PEG and 5 or 6 capsules, enough to use withone 500 ml bottle of water. The kit would also have a 500-600 ml cup formixing, and also a product DVD/CD-ROM that goes over the prep in detailand also has a FAQ (frequently asked questions) section if people arehaving trouble using the kit.

Step One:

Ingest a low residue diet (basically, no fruits, nuts, or vegetables)beginning 3 to 5 days prior to procedure (this is common to most GIpractices, for all preps).

Step Two:

Ingest a low residue breakfast the morning of prep day (again, this isstandard for almost all preps).

Step Three:

Ingest a clear liquid lunch (juices, jello, tea, coffee) mid-day on theprep day.

Step Four:

Begin at 3 PM to 4 PM to ingest the kit as follows:

-   Dissolve one 29.5 gram packet of PEG in 500 ml water-   You may add Crystal light if you desire-   Drink 500 ml of solution over 30 to 60 minutes-   Consume 5 or 6 capsules during the 30 to 60 minutes that you consume    the solution. One capsule every 5 to 10 minutes seems to be    adequate.-   Repeat Step four as above until you have ingested all 8 packets of    PEG and all 44 capsules over the next 4 to 8 hours.-   You may slow the rate of consumption if you feel bloated. Bloating    tends to go away once you start passing stool.

This kit may be administered in a split dose format as well, withone-half to three-quarters of the kit being consumed on the day prior tothe procedure, and the remaining one-half to one-quarter of the kitbeing consumed in the following morning, the day of the procedure.

The second product, Hi-PEG, is used as follows and is quite similar inits use:

Contents of Hi-PEG kit (differences from Lo-PEG are in bold):

8 Packets of PEG 3350, each containing 52.5 grams of PEG 3350

20 capsules, each containing:

Sodium bicarbonate, 0.286 grams per capsule

Sodium chloride, 0.56 grams per capsule

Potassium chloride, 0.074 grams per capsule

(note that no sodium sulfate is used in the Hi-PEG formulation)

Step One:

Ingest a low residue diet (basically, no fruits, nuts, or vegetables)beginning 3 to 5 days prior to procedure (this is common to most GIpractices, for all preps).

Step Two:

Ingest a low residue breakfast the morning of prep day.

Step Three:

Ingest a clear liquid lunch (juices, jello, tea, coffee) mid-day on theprep day.

Step Four:

Begin at 3 PM to 4 PM to ingest the kit as follows:

-   Dissolve one 52.5 gram packet of PEG in 500 ml water-   You may add Crystal light if you desire-   Drink 500 ml of solution over 30 to 60 minutes-   Consume 2 or 3 capsules during the 30 to 60 minutes that you consume    the solution. One capsule every 10 to 20 minutes seems to be    adequate.-   Repeat Step four as above until you have ingested all 8 packets of    PEG and all 20 capsules over the next 4 to 8 hours.-   You may slow the rate of consumption if you feel bloated. Bloating    tends to go away once you start passing stool. Some people stop    drinking when they are bloated until they have a bowel movement,    then resume drinking once the bloating is relieved. This practice is    fine.

This kit may be administered in a split dose format as well, withone-half to three-quarters of the kit being consumed on the day prior tothe procedure, and the remaining one-half to one-quarter of the kitbeing consumed in the following morning, the day of the procedure.

1. A kit comprising: a) one or a plurality of unit doses of an osmoticagent; b) one or a plurality of unit doses of a composition comprisingelectrolytes.
 2. The kit of claim 1, further comprising a plurality offlavor packs.
 3. The kit to claim 1, further comprising a plurality ofcontainers wherein the one or a plurality of unit doses of osmotic agentare contained within at least one of said containers.
 4. The kit ofclaim 3, where the containers additionally contain one or a plurality ofunits of flavor packs.
 5. (canceled)
 6. The kit of claim 1, wherein theosmotic agent is PEG having average molecular weight between 2000 and8000.
 7. (canceled)
 8. The kit of claim 1, wherein the electrolytes areindependently selected from the group consisting of sodium sulfate,sodium bicarbonate, sodium chloride, potassium chloride, magnesiumsulfate, magnesium citrate, ascorbic acid, and sodium ascorbate. 9.(canceled)
 10. The kit of claim 8, wherein the electrolyte doses are ina pill, tablet, capsule, gel-cap, micro-encapsulated granules, or liquidform.
 11. (canceled)
 12. The kit of claim 1, wherein the electrolytedose comprises: from 0.2 g to 20 g sodium chloride; from 0.1 g to 5 gpotassium chloride; and from 0.1 g to 10 g sodium bicarbonate.
 13. Thekit of claim 12, further comprising from 0.1 g to 40 g sodium sulfate.14. The kit of claim 12, wherein the electrolyte doses are in a pill,tablet, gel-cap, micro-encapsulated granules, or capsule form and theelectrolyte dose comprises from 0.5 g to 1 g sodium chloride; from 0.2 gto 0.5 g potassium chloride; from 0.7 g to 1 g sodium bicarbonate; andfrom 0.1 g to 4 g sodium sulfate.
 15. (canceled)
 16. The kit of claim 6,wherein the electrolyte doses are in a pill, tablet, capsule, gel-cap,micro-encapsulated granules, or liquid form and wherein a unit dose ofPEG is from 20 g to 175 g of PEG
 3350. 17-19. (canceled)
 20. A capsule,pill, gel-cap, micro-encapsulated granules, or a tablet which comprisessodium chloride, potassium chloride and sodium bicarbonate.
 21. Thecapsule, pill, gel-cap, micro-encapsulated granules, or a tablet ofclaim 20, further comprising sodium sulfate.
 22. The capsule, pill,gel-cap, or micro-encapsulated granules, or a tablet of claim 20,wherein the capsule, pill, gel-cap, micro-encapsulated granules, or atablet comprise from 0.08 g to 1.7 g sodium chloride; from 0.03 g to0.25 g potassium chloride; and from 0.1 g to 0.9 g sodium bicarbonate.23. The capsule, pill, gel-cap, micro-encapsulated granules, or a tabletof claim 22 further comprising from 0.35 g to 1.6 g sodium sulfate. 24.A method for preparing a subject for a colon-related procedurecomprising: a) providing a plurality of individually packaged osmoticagent doses and a plurality of individually packaged electrolyte doses;b) dissolving one or more of said plurality of osmotic agent doses inwater; c) administering one or more of said plurality of osmotic agentdoses dissolved in water to said subject; d) administering one or moreof said plurality of electrolyte doses to said subject; and e) repeatingsteps (b)-(d) until all of said plurality of osmotic agent doses and allof said plurality of electrolyte doses have been ingested by saidsubject.
 25. The method of claim 24, further comprising the step ofpassing stool from the colon of said subject.
 26. The method of claim25, further comprising the step of analyzing said stool.
 27. The methodof claim 24, further comprising the step of performing a diagnostic orsurgical procedure on said subject.
 28. The method of claim 24, whereinsaid osmotic agent doses and a plurality of individually packagedelectrolyte doses are those of any of claims 1 through 23.